ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Adenosine triphosphate(ATP)production in cardio-myocytes in healthy heart depends primarily on the oxidative phosphorylation of fatty acids and,to a lesser extent,on the oxi-dation or glycolysis of glucose.Patients with heart failure devel-op severe disturbances in energy metabolism,including disturb-ances in substrate uptake and utilization,oxidative phosphoryla-tion,and ATP shuttling,resulting in inadequate cardiac energy supply.By intervening in energy metabolism pathways,cardiac efficiency can be increased,energy production deficits can be reduced,and cardiac function can be improved in patients with heart failure.We hence have reviewed and outlined the mecha-nisms and therapeutic implications of metabolic changes during heart failure.

The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

Objective:To investigate the effects of Ziyin Liangxue formula combined with prednisone on immune function and the ST2/IL-33 pathway in mice with immune thrombocytopenia.Methods:In 40 BALB/c mice,32 were constructed as immune thrombocytopenia mouse models by antiplatelet serum injection.After successful modeling,the mice were randomly divided into model group,Ziyin Liangxue formula group(0.2 ml/10 g),prednisone group(0.2 ml/10 g),and Ziyin Liangxue formula+prednisone group(0.2 ml/10 g),8 mice in each group,and the other 8 mice were set as control group.The drugs were administered by gavage at the dose,and the model group and control group were given equal amounts of saline by gavage once a day for 2 weeks of continuous intervention.Blood samples and spleen tissues were collected,the peripheral platelet count was measured by automatic hematology analyzer,the pathological changes in spleen tissue was observed by HE staining,the levels of serum transforming growth factor(TGF)-β,interleukin(IL)-17,and peripheral blood thrombopoietin(TPO)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of IL-33,sST2,and ST2 in spleen tissue was detected by Western blot,and the cell counts of peripheral blood Th17 and Treg were detected by flow cytometry.Results:Compared with the control group,the number of platelets,the level of TPO,TGF-β,and Treg cells were significantly decreased(P＜().05),while the level of IL-17,Thl7 cells,and the expression of IL-33,sST2,and ST2 protein were significantly increased in the model group(P＜0.01).Compared with the model group,the number of platelets,the level of TPO,TGF-β,and Treg cells were significantly increased(P＜0.05),while the level of IL-17,Th17 cells,and the expression of IL-33,sST2,and ST2 protein were significantly decreased in the Ziyin Liangxue formula+prednisone group(P＜0.01).Conclusion:Ziyin Liangxue formula+prednisone can effectively regulate Th17/Treg balance,thus effectively improve immune thrombocytopenia,and the mechanism may be related to the regulation of ST2/IL-33 signaling pathway.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To prepare mesenchymal stem cells with antioxidant capacity (AO-MSC ) from human umbilical cords and evaluate its cell biological properties.Methods:In control group,mesenchymal stem cells (MSC) were isolated by digesting human umbilical cord Wharton's Jelly tissues with 0.2％ collagenase Ⅱ,and the released cells were collected and cultured in an animal serum-free culture medium.In AO-MSC group,incompletely collagenase Ⅱ-digested tissue debris were allowed to adhere to flusk flat bottoms and the AO-MSC was harvested by adherent culture. The conventional digestion and culture method was used as control.MSC colony forming ability was evaluated by fibroblast colony forming assay (CFU-F).MSC proliferative capacity was evaluated by CCK-8 assay.The MSC surface markers were detected by using flow cytometry and immunofluorescence staining.The adipogenic and osteogenic capacity of MSC was evaluated by multi-differentiation in vitro,and the mRNA expression of genes that control adipogenic and osteogenic differentiation was detected by real-time fluorescence quantitative PCR (RT-qPCR );Moreover,the mRNA expression of antioxidant substances such as SOD-1,GSH,GAT,and NQO1 in MSC was also evaluated by RT-qPCR.Results:The AO-MSC isolated by this strategy reached a confluence of 80％-90％ at around 18 days and grew in a swirling pattern.Flow cytometry and immunofluorescence staining assays showed that CD73,CD29,CD105,CD90 were highly expressed and CD31,CD45,HLA-DR were scarcely expressed in AO-MSC.AO-MSC exhibited stronger self-renewal and differentiation ability compared to MSC.However,the in vitro adipogenic-osteogenic capacity of MSC in the control group was stronger than that of AO-MSC.RT-qPCR assay showed that AO-MSC expressed higher mRNA levels of antioxidant substances compared to MSC.Conclusion:Human AO-MSC is successfully prepared from human umbilical cord without animal serum.

Objective:To investigate the safety and clinical effect of testis-sparing microsurgery(TSMS)in the treatment of benign testis tumor(BTT).Methods:We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023.The median age of the patients was 23 years.All the tumors were unilateral,7 in the left and 9 in the right side,with a median diameter of 1.85 cm(1.0-3.5 cm).The patients all underwent color Doppler flow imaging(CDFI),MRI,semen analysis and examination of serum T,alpha-fetoprotein(AFP),human chorionic gonadotropin(HCG)and lactate dehydrogenase(LDH),followed by TSMS.The boundaries between the tumors and normal testis tissue were accurately identified under the microscope,and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely.Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue.The resected specimens were subjected to fast frozen pathology intraoperatively,and the patients were followed up for 14-40 months by regular scrotal CDFI,MRI and examinations of serum T and semen parameters.Results:The levels of serum T,AFP,HCG and LDH and semen parameters were all within the normal range preoperatively.TSMS were successfully completed in all the cases,and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors:Urinary and Male Genital Tumors.CDFI showed normal blood supply within the testis tissue at 1 month after surgery.No signs of intra-testicu-lar tumor residue,recurrence or metastasis,nor significant changes in the levels of serum T,AFP,HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline.Natural conception was achieved in 2 cases at 16 and 18 months re-spectively after surgery.Conclusion:BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histo-pathology.TSMS can achieve complete excision of the tumor,maximal sparing of the normal testis tissue and thereby effective preserva-tion of male fertility.

Cardiovascular disease(CVD)has become a significant public health issue both domestically and globally.This article summarizes the role and predictive value of brachial ankle pulse wave velocity(baPWV)in CVD,the relationships between baPWV and CVD risk factors such as age,blood pressure,heart rate,dyslipidemia,diabetes and chronic kidney disease etc.,and the latest threshold value and limitations of baPWV.These findings may pro-vide a theoretical basis for the use of baPWV as a screening tool for the prevention and treatment of arteriosclerosis and CVD in large populations.Additionally,it suggests that it's a very important and feasible goal to early screen and manage potential CVD patients or CVD patients.

Objective To explore the optimal morning discharge time and pipeline disinfection frequency of the fi-nal rinse water from the endoscopy center according to the microbial culture results.Methods Different morning discharge timing and number of bacterial colonies in the pipeline for the final rinse water from the endoscopy center of a hospital in Jiangsu Province were monitored.Microbial detection was conducted on water samples collected from the two final rinse water sampling sites in the endoscopy room after 0,1,3,5,and 7 minutes of discharge,respec-tively(100 mL each,continuously monitored for 35 days,with 70 samples at each time point)to explore the optimal discharge timing.The optimal disinfection frequency of pipelines for purified water was explored according to the determined optimal morning discharge timing.Two samples were taken daily from 2 sampling sites after pipeline disinfection and continued for 5 weeks,resulting in 70 samples in total.Results Sampling and monitoring of the fi-nal rinse water at different morning discharge time points showed that the median numbers of bacterial colonies at 0,1,3,5,and 7 minutes were 745.00(373.00,1 452.50),150.00(96.75,235.75),44.00(38.00,48.00),12.00(5.00,18.00),and 6.00(4.00,9.00)CFU/100 mL,respectively.Except the difference between the 5 minute group and the 7 minute group(P＞0.05),differences among all the other groups were statistically significant(all P＜0.05).The median of the 0,1,3,and 5 minute groups was＞10 CFU/100 mL,while the median of the 7 mi-nute group was＜10 CFU/100 mL,within the qualified range.The discharge time was therefore determined to be 7 minutes.The average numbers of bacterial colonies from the final rinse water samples taken at different time points after pipeline disinfection(1,2,3,4,and 5 weeks after disinfection)were(4.21±0.86),(4.43±0.71),(6.00±0.56),(6.43±0.45),and(13.57±1.03)CFU/100 mL,respectively.The qualification rates of pipeline in terms of bacterial colony were 100％,100％,100％,100％,and 28.57％,respectively.The differences of average num-bers of bacterial colonies from the final rinse water samples taken at different time points after pipeline disinfection were statistically significant(P＜0.001).The average number of bacterial colonies 5 weeks after pipeline disinfec-tion was different from those after 1,2,3,and 4 weeks,with statistically significant differences(all P＜0.05),while no statistically significant differences among the other groups were observed(all P＞0.05).The optimal disin-fection frequency for the purified water pipeline was once every 4 weeks.Conclusion The final rinse water remai-ning in the terminal of pipeline is contaminated to a certain degree.It is recommended to discharge water in the morning for 7 minutes before using it,and disinfect the purified water pipeline every 4 weeks.